The central goal of this project will be to develop active interfaces between arrays of addressable nanowire[unreadable] electronic devices and cells to create two- and three-dimensional functional biomaterials. The nanoscale[unreadable] represents a natural length scale for devices used to create active interfaces to cells because biological[unreadable] nanostructures are the key components that define intercellular communication and signaling in living systems,[unreadable] yet this scale of interface is virtually uncharted research territory. The overall objectives that will be explored to[unreadable] address this territory and to meet the central project goal are as follows. First, limits of nanowire nanoelectronic[unreadable] device/cell interface functionality and sensitivity will be characterized. Communication with cells, both recording[unreadable] from (cell output) and stimulation of (cell input), through direct electrical mechanisms and chemical/biological[unreadable] signal detection/release will be developed and the corresponding detection sensitivity and spatial resolution for[unreadable] different modes will be elucidated. Second, addressable arrays of different types of functional nanowire[unreadable] devices interfaced with cellular networks will be developed and their behavior delineated. An important[unreadable] emphasis of this work, which exploits the unique capabilities of bottom-up versus top-down nanoscience, will[unreadable] be to develop (i) interfaced nanoelectronic arrays on flexible, biocompatible polymeric substrates, (ii) folded or[unreadable] layered nanowire/cell three-dimensional arrays using perforated polymeric substrates to enhance layer-to-layer[unreadable] interactions, and (iii) nanoelectronic devices projecting out of the substrate plane to enable interfacing `into'[unreadable] three-dimensional cellular arrays and tissue. The proposed project has the potential to impact biomedical[unreadable] research in substantial ways, including the establishment of powerful new tools for understanding the[unreadable] behavior of interacting cellular networks, the development of sophisticated, electrically-based cell/tissue[unreadable] interfaces for prosthetics and other medical devices, and the creation of new biomaterials with potential for[unreadable] diverse applications, such as in hybrid information processing.